Journal Article

Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA

Ranhui Duan, ChangHui Pak and Peng Jin

in Human Molecular Genetics

Volume 16, issue 9, pages 1124-1131
Published in print May 2007 | ISSN: 0964-6906
Published online March 2007 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddm062
Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA

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MicroRNAs (miRNAs) are small non-coding RNAs that inhibit expression of specific target genes at the post-transcriptional level. Sequence variations in miRNA genes, including pri-miRNAs, pre-miRNAs and mature miRNAs, could potentially influence the processing and/or target selection of miRNAs. In this study, we have systematically identified single nucleotide polymorphisms (SNPs) associated with 227 known human miRNAs. Among 323 total SNPs that we identify, 12 are located within the miRNA precursor and one is at the eighth nucleotide (+8) of the mature miR-125a, which has been proposed to play a critical role in recognition of mRNA targets by miRNAs. Through a series of in vivo analyses, we unexpectedly find that this miR-125a SNP significantly blocks the processing of pri-miRNA to pre-miRNA, in addition to reducing miRNA-mediated translational suppression. Thus, our study reveals an additional structural requirement for pri-miRNA processing and emphasizes the importance of identifying new miRNA SNPs and their contributions to miRNA biogenesis and human genetic disease.

Journal Article.  3476 words.  Illustrated.

Subjects: Genetics and Genomics

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